The goal of this Mentored Research Scientist Development Award (K01) is to prepare Dr. Kathryn Demos for a career as an independent scientist, conducting translational research investigating neural mechanisms in obesity and weight loss. Combining didactic training, mentorship by a highly qualified team of established scientists, and the first-hand experience of conducting the proposed research, Dr. Demos will gain extensive training in the areas of (1) obesity and behavioral weight loss intervention, [(2) statistics and research design,] (3) neuroeconomics and decision-making, (4) executive function and brain imaging in a clinical population, (5) the responsible conduct of research, and (6) professional development. Throughout the course of the award Dr. Demos will work closely with her primary mentor, Dr. Rena Wing, and her multidisciplinary team of co- mentors, [Dr. Eduardo Nillni (pathophysiology of obesity), Dr. Hernando Ombao (statistics),] Dr. Antonio Rangel (neuroeconomics), and Drs. Ronald Cohen and Lawrence Sweet (executive function and brain imaging). Complementing her previous graduate and post-doctoral training in cognitive neuroscience and functional magnetic resonance imaging (fMRI), the mentorship provided by this expert team coupled with the premier behavioral weight loss treatment program and facility run by Dr. Wing at the Miriam Hospital/Brown University Medical School, will provide Dr. Demos with the necessary experience and resources to carry out this innovative research and achieve her career goals. Dr. Demos'long-term career goals include developing a translational research program from brain science to weight loss treatment, and to understand the neural and behavioral basis of how and why people gain, lose, and successfully control weight. Obesity is one of the most important public health issues today, contributing to many of the primary causes of morbidity and mortality in the United States, including cardiovascular disease, diabetes, and certain cancers. At the same time, treatment remains difficult and many individuals continually struggle to lose or maintain excess weight. Many studies have investigated the eating behaviors of obese individuals as well as those who have successfully lost weight, yet little work has been done to try to understand how individuals decide to choose healthy foods like fruits and vegetables over good-tasting foods like chocolate and pizza and what brain processes support this. Thus in the proposed studies, Dr. Demos will begin by investigating the neural basis of food choice decision-making in females who are obese (N=30), have successfully lost weight and maintained it [(N=20)], and normal weight (NW) controls [(N=20)]. Participants will undergo event-related fMRI while performing a food choice decision-making task to determine whether these groups differ in their behavior or brain activity when they make food choice decisions. [Additionally, resting-state functional connectivity (rs- fcMRI) will be measured in order to determine how brain regions involved in reward processing and self-control form networks and are functionally connected.] Subsequently, the 30 obese participants will be enrolled in a behavioral weight loss intervention and re-scanned after treatment to determine whether participating in a behavioral weight loss program is associated with behavioral and neural changes in food choice decision- making. Through the proposed research Dr. Demos will gain the necessary training and experience to achieve her goal of becoming an independent investigator by acquiring a strong foundation in obesity and behavioral weight loss treatment, statistics and research design, neuroeconomics, and executive function in obesity. This project will provide new insights into the role of decision-making in obesity and its neural underpinnings, and will lead to innovative approaches in the clinical treatment of obesity. PUBLIC HEALTH RELEVANCE: This project is designed to develop a programmatic line of research for Dr. Demos and assist her in emerging as an independent investigator. Through didactic training and mentoring, Dr. Demos will develop proficiency in (1) obesity and behavioral weight loss intervention, (2) statistics and research design, (3) neuroeconomics, and (4) executive function and fMRI in obesity, (5) the responsible conduct of research, and (6) skills needed for professional development. The proposed research project uses functional neuroimaging to determine whether successful weight loss maintainers or obese individuals differ from normal weight individuals in their food choice decision-making and whether the brain patterns of obese individuals on the food decision task change after participating in a behavioral weight loss program.